{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T11:54:41Z","timestamp":1790855681824,"version":"4.1.0"},"reference-count":22,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"vor","delay-in-days":30,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100005610","name":"Fukuoka University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005610","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["iubmb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["BioFactors"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Skin aging is characterized by impaired extracellular matrix (ECM) synthesis and increased inflammatory signaling in dermal fibroblasts. Notably, ubiquinol\u201010 (UqH\u201010), the reduced form of coenzyme Q10 (ubiquinone\u201010, Uq\u201010), supports mitochondrial function and reduces oxidative stress, but its dermal levels decrease with aging. The topical efficacy of UqH\u201010 is limited by its physicochemical properties, including oxidative instability, photo instability, and phototoxicity. This study aimed to evaluate the anti\u2010aging potential of esterified UqH\u201010 derivatives\u2014UqH 1,4\u2010bis\u2010hemi\u2010succinate (UqH\u2010SUC) and UqH 1,4\u2010bis\u2010hemi\u2010glutarate (UqH\u2010GLUT)\u2014in human dermal fibroblasts. Normal human dermal fibroblasts (NHDFs) were treated with Uq\u201010, UqH\u201010, or their derivatives (100\u2009\u03bcM) for 48\u2009h. Intracellular Uq\u201010 and UqH\u2010derivatives were quantified by LC\u2013MS\/MS, while ATP levels and viability were measured using luminescence\u2010 and fluorescence\u2010based assays. Gene and protein expression of ECM components, matrix metalloproteinases (MMP1, MMP3), and SASP markers (IL6, IL8, p21) were analyzed by qPCR, ELISA, western blotting, and immunofluorescence. Additional experiments were conducted in the presence of an ascorbic acid derivative to evaluate pro\u2010COL1A1 production. We found that UqH\u2010SUC markedly increased intracellular Uq\u201010 and UqH\u201010 (2.1\u2010fold vs. Uq\u201010; 8.3\u2010fold vs. UqH\u201010), enhanced ATP production, suppressed SASP factors, and upregulated ECM components including COL1A1, elastin, and hyaluronic acid. Despite its minimal conversion to UqH\u201010, UqH\u2010GLUT accumulated intracellularly, reduced SASP expression, and downregulated MMPs. Co\u2010treatment with UqH\u2010SUC and phosphorylated ascorbic acid derivatives significantly enhanced extracellular COL1A1 secretion while lowering intracellular retention. Moreover, esterified UqH\u201010 derivatives, particularly UqH\u2010SUC, enhance mitochondrial function, modulate fibroblast senescence, and stimulate ECM synthesis. Moreover, their combination with ascorbic acid derivatives provides a promising strategy for skin anti\u2010aging intervention.<\/jats:p>","DOI":"10.1002\/biof.70154","type":"journal-article","created":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T10:55:36Z","timestamp":1790852136000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Enhanced Extracellular Matrix Synthesis\u2013Related Responses Induced by Ubiquinol\u201010 Derivatives in Human Dermal Fibroblasts"],"prefix":"10.1002","volume":"52","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8475-5595","authenticated-orcid":false,"given":"Shotaro","family":"Goto","sequence":"first","affiliation":[{"name":"Faculty of Pharmaceutical Sciences Fukuoka University  Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masako","family":"Harada","sequence":"additional","affiliation":[{"name":"Faculty of Pharmaceutical Sciences Fukuoka University  Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3482-4510","authenticated-orcid":false,"given":"Shuichi","family":"Setoguchi","sequence":"additional","affiliation":[{"name":"Faculty of Pharmaceutical Sciences Fukuoka University  Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-3289-757X","authenticated-orcid":false,"given":"Kazuhisa","family":"Matsunaga","sequence":"additional","affiliation":[{"name":"Faculty of Pharmaceutical Sciences Fukuoka University  Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiro","family":"Takata","sequence":"additional","affiliation":[{"name":"Faculty of Pharmaceutical Sciences Fukuoka University  Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,1]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"crossref","first-page":"112559","DOI":"10.1016\/j.exger.2024.112559","article-title":"Role of Fibroblast Autophagy and Proliferation in Skin Anti\u2010Aging","volume":"196","author":"Lu Y.","year":"2024","journal-title":"Experimental Gerontology"},{"key":"e_1_2_11_3_1","doi-asserted-by":"crossref","first-page":"1325","DOI":"10.3390\/antiox10081325","article-title":"Role of Coenzyme Q10 in Health and Disease: An Update on the Last 10\u2009Years (2010\u20132020)","volume":"10","author":"Cirilli I.","year":"2021","journal-title":"Antioxidants"},{"key":"e_1_2_11_4_1","doi-asserted-by":"crossref","first-page":"520","DOI":"10.3390\/antiox10040520","article-title":"Metabolic Targets of Coenzyme Q10 in Mitochondria","volume":"10","author":"Hidalgo\u2010Guti\u00e9rrez A.","year":"2021","journal-title":"Antioxidants"},{"key":"e_1_2_11_5_1","first-page":"50","article-title":"The Role of Coenzyme Q10 in Skin Aging and Opportunities for Topical Intervention: A Review","volume":"17","author":"Lain E. T.","year":"2024","journal-title":"Journal of Clinical and Aesthetic Dermatology"},{"key":"e_1_2_11_6_1","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1007\/s11357-005-1632-z","article-title":"Coenzyme Q\u2010Dependent Functions of Plasma Membrane in the Aging Process","volume":"27","author":"Navas P.","year":"2005","journal-title":"Age (Dordrecht, Netherlands)"},{"key":"e_1_2_11_7_1","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1038\/s41586-019-1707-0","article-title":"FSP1 Is a Glutathione\u2010Independent Ferroptosis Suppressor","volume":"575","author":"Doll S.","year":"2019","journal-title":"Nature"},{"key":"e_1_2_11_8_1","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1002\/biof.5520090238","article-title":"Coenzyme Q10, a Cutaneous Antioxidant and Energizer","volume":"9","author":"Hoppe U.","year":"1999","journal-title":"BioFactors"},{"key":"e_1_2_11_9_1","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1111\/j.1473-2165.2006.00220.x","article-title":"Anti\u2010Inflammatory Effects of CoQ10 and Colorless Carotenoids","volume":"5","author":"Fuller B.","year":"2006","journal-title":"Journal of Cosmetic Dermatology"},{"key":"e_1_2_11_10_1","doi-asserted-by":"crossref","first-page":"247","DOI":"10.3164\/jcbn.20-185","article-title":"Protective Effects of Coenzyme Q10 on Cell Damage Induced by Hydrogen Peroxides in Cultured Skin Fibroblasts","volume":"69","author":"Mine Y.","year":"2021","journal-title":"Journal of Clinical Biochemistry and Nutrition"},{"key":"e_1_2_11_11_1","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1038\/s41538-025-00465-0","article-title":"Enhanced Solubility and Bioavailability of Coenzyme Q10 via Co\u2010Amorphous System Using Stevioside","volume":"9","author":"Luo Y.","year":"2025","journal-title":"npj Science of Food"},{"issue":"1","key":"e_1_2_11_12_1","doi-asserted-by":"crossref","first-page":"20","DOI":"10.3109\/03639045.2011.650648","article-title":"Preparation of Coenzyme Q10 Nanostructured Lipid Carriers for Epidermal Targeting With High\u2010Pressure Microfluidics Technique","volume":"39","author":"Chen S.","year":"2013","journal-title":"Drug Development and Industrial Pharmacy"},{"issue":"1","key":"e_1_2_11_13_1","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.ijpharm.2010.05.006","article-title":"Preparation and Characterization of Liposomal Coenzyme Q10 for In\u00a0Vivo Topical Application","volume":"395","author":"Lee W. C.","year":"2010","journal-title":"International Journal of Pharmaceutics"},{"key":"e_1_2_11_14_1","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1002\/biof.1678","article-title":"Evaluation of Photostability and Phototoxicity of Esterified Derivatives of Ubiquinol\u201010 and Their Application as Prodrugs of Reduced Coenzyme Q10 for Topical Administration","volume":"46","author":"Setoguchi S.","year":"2020","journal-title":"BioFactors"},{"key":"e_1_2_11_15_1","doi-asserted-by":"crossref","first-page":"1817","DOI":"10.3390\/polym14091817","article-title":"Anti\u2010Inflammatory and Pro\u2010Regenerative Effects of Hyaluronan\u2010Chitlac Mixture in Human Dermal Fibroblasts: A Skin Ageing Perspective","volume":"14","author":"Donato A.","year":"2022","journal-title":"Polymers"},{"key":"e_1_2_11_16_1","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1007\/s00253-024-13021-9","article-title":"Recombinantly Expressed rhFEB Remodeled the Skin Defect of Db\/Db Mice","volume":"108","author":"Li X.","year":"2024","journal-title":"Applied Microbiology and Biotechnology"},{"key":"e_1_2_11_17_1","doi-asserted-by":"crossref","first-page":"29","DOI":"10.3164\/jcbn.20-187","article-title":"Stimulatory Effects of Collagen Production Induced by Coenzyme Q10 in Cultured Skin Fibroblasts","volume":"71","author":"Mine Y.","year":"2022","journal-title":"Journal of Clinical Biochemistry and Nutrition"},{"key":"e_1_2_11_18_1","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1002\/biof.5520320128","article-title":"Mechanisms of Inhibitory Effects of CoQ10 on UVB\u2010Induced Wrinkle Formation In\u00a0Vitro and In\u00a0Vivo","volume":"32","author":"Inui M.","year":"2008","journal-title":"BioFactors"},{"key":"e_1_2_11_19_1","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1002\/biof.56","article-title":"Coenzyme Q10 Protects Against Oxidative Stress\u2010Induced Cell Death and Enhances the Synthesis of Basement Membrane Components in Dermal and Epidermal Cells","volume":"35","author":"Muta\u2010Takada K.","year":"2009","journal-title":"BioFactors"},{"key":"e_1_2_11_20_1","doi-asserted-by":"crossref","first-page":"39819","DOI":"10.1074\/jbc.M110.161547","article-title":"Neprilysin Is Identical to Skin Fibroblast Elastase: Its Role in Skin Aging and UV Responses","volume":"285","author":"Morisaki N.","year":"2010","journal-title":"Journal of Biological Chemistry"},{"key":"e_1_2_11_21_1","doi-asserted-by":"crossref","first-page":"8475","DOI":"10.3390\/ijms21228475","article-title":"Coenzyme Q10 Efficacy Test for Human Skin Equivalents Using a Pumpless Skin\u2010On\u2010A\u2010Chip System","volume":"21","author":"Kim J.","year":"2020","journal-title":"International Journal of Molecular Sciences"},{"key":"e_1_2_11_22_1","first-page":"1029","article-title":"Combination of Glycinamide and Ascorbic Acid Synergistically Promotes Collagen Production and Wound Healing in Human Dermal Fibroblasts","volume":"10","author":"Lee J. E.","year":"2022","journal-title":"Biomedicine"},{"key":"e_1_2_11_23_1","doi-asserted-by":"crossref","first-page":"e21219","DOI":"10.1096\/fj.202001564RR","article-title":"Collagen Release by Human Hepatic Stellate Cells Requires Vitamin C and Is Efficiently Blocked by Hydroxylase Inhibition","volume":"35","author":"Smith\u2010Cortinez N.","year":"2021","journal-title":"FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology"}],"container-title":["BioFactors"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/iubmb.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/biof.70154","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/iubmb.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/biof.70154","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/iubmb.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/biof.70154","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T10:55:39Z","timestamp":1790852139000},"score":1,"resource":{"primary":{"URL":"https:\/\/iubmb.onlinelibrary.wiley.com\/doi\/10.1002\/biof.70154"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9]]},"references-count":22,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2026,9]]}},"alternative-id":["10.1002\/biof.70154"],"URL":"https:\/\/doi.org\/10.1002\/biof.70154","archive":["Portico"],"relation":{},"ISSN":["0951-6433","1872-8081"],"issn-type":[{"value":"0951-6433","type":"print"},{"value":"1872-8081","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9]]},"assertion":[{"value":"2026-02-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-11","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-01","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70154"}}